Seasonal Influenza Vaccine Safety: A Summary for Clinicians
- Seasonal influenza vaccination is the most important way of preventing seasonal influenza virus infections and potentially severe complications, including death. Seasonal influenza vaccination reduces the likelihood of becoming ill with influenza or transmitting influenza to others.
- The 2012-2013 seasonal influenza vaccine protects against an influenza A H3N2 virus, an influenza B virus, and the 2009 H1N1 virus; initial doses of licensed vaccine are expected to be available by late August 2012.
- Two types of seasonal influenza vaccine are licensed by the Food and Drug Administration (FDA) for use in the United States: trivalent inactivated influenza vaccine (TIV) and live, attenuated influenza vaccine (LAIV).
- Both seasonal LAIV and TIV contain three strains of influenza viruses: one influenza A (H3N2) virus, one influenza A (H1N1) virus, and one influenza B virus. Each year, before influenza season starts, one or more virus strains in the vaccine might be changed on the basis of global surveillance for influenza viruses and the emergence and spread of new strains.
- TIV is injected into the muscle of the upper arm or thigh. It can be used for healthy people who are 6 months of age or older, and it can be used in people with chronic medical conditions and women who are pregnant. Healthy people are defined as people who do not have an underlying medical condition that predisposes them to influenza complications. Several TIV products are licensed for use in the United States (see Table 2 of 2012-2013 ACIP Seasonal Influenza Recommendations).2
- LAIV is given as a nasal spray. It can be used for healthy people 2-49 years of age who are not pregnant.
- Influenza vaccines, like any medical product, carry some risks but serious adverse events after influenza vaccination are uncommon.
- Adverse events after vaccination may be causally related to vaccine or may be coincidental.
- When seasonal influenza vaccines are administered according to the licensed indication and usage information, they are safe.
- All seasonal influenza vaccines licensed in the United States are produced in eggs and they do not contain adjuvants. Some multidose TIV preparations contain thimerosal which is used as a preservative to prevent bacterial growth.
CDC and FDA routinely monitor the safety of all vaccines licensed in the United States, including seasonal influenza vaccines. This summary provides the following information on seasonal influenza vaccines:
- Safety of TIV and LAIV, including adverse events, contraindications and precautions, screening, and safe vaccine administration;
- The Vaccine Adverse Event Reporting System (VAERS); and
- Additional resources for clinicians about influenza vaccines and vaccine safety.
Trivalent Inactivated Influenza Vaccine (TIV)
Studies support the safety of annual TIV vaccination in children and adults. TIV is administered as an injection and may cause reactions at the injection site, such as pain, redness, and swelling. Systemic events can occur after TIV but are usually mild and self-limited. TIV (which contains inactivated virus) cannot cause influenza. More information about TIV safety is provided below:
- The most frequent reactions reported after vaccination in children and adults are pain and other injection-site reactions. Up to 64% of people vaccinated with TIV experience pain at the injection site, which usually resolves in <2 days without treatment.3
- Fever, malaise, myalgia, and other systemic symptoms that can occur after vaccination with TIV most often affect persons who have had no previous exposure to the influenza virus antigens in the vaccine (e.g., young children). In adults the rate of having these events is similar after TIV and after a placebo vaccine.1
- Ocular or respiratory symptoms (e.g., red eyes, hoarse voice, cough) have occasionally been reported within 24 hours after TIV administration in some studies, but are typically mild and resolve quickly without specific treatment.1
- Vaccine components can rarely cause true allergic reactions, also called immediate hypersensitivity reactions, among certain recipients. Symptoms of immediate hypersensitivity range from mild urticaria (hives) and angioedema (swelling beneath the skin) to anaphylaxis.1,4
- In a study of more than 250,000 children aged <18 years, the investigators did not identify risk for any clinically important adverse events after TIV.‡5
- Another study evaluated adverse events in adults across 15 years and showed that reporting rates for adverse events after TIV were reasonably consistent over time. This study did not identify any new safety concerns.§6
- During the 2010-2011 influenza season, CDC studied the healthcare visit records of more than 200,000 vaccinated children 6 months through 4 years of age through its Vaccine Safety Datalink project. The analyses found that febrile seizures following TIV and pneumococcal conjugate vaccines given to this age group were rare, but did occur at higher than expected rates. The febrile seizures were most common in children ages 12 through 23 months when the two vaccines were given during the same healthcare visit. In this group, about one additional febrile seizure occurred among every 2,000 to 3,000 children vaccinated. After thoroughly evaluating the available information, CDC determined that no changes in the childhood immunization schedule were necessary.7
- Temporally associated Guillain–Barré Syndrome (GBS) cases following influenza vaccination have been observed/reported; gastrointestinal and upper respiratory infections are known risk factors for GBS, which is a serious neurological condition that can cause paralysis.
- Safety monitoring of seasonal influenza vaccines over the course of many years has not detected a clear link to Guillain-Barré Syndrome (GBS). However, if there is a risk of GBS from current flu vaccines, it would be no more than 1 or 2 cases per million people vaccinated.1 This is much lower than the risk of severe influenza, which can be prevented by vaccination.
- Each year, about 3,000 to 6,000 people in the United States develop GBS whether or not they received a vaccination — that’s 1 to 2 people out of every 100,000 people.
- For comparison, an estimated 750 per million adults are hospitalized with seasonal influenza each year; many of these cases could be prevented by vaccination. In addition, studies suggest that the risk of developing GBS after having influenza is higher than the potential risk of developing GBS after vaccination.1
Contraindications for TIV
TIV should not be administered to the following:1
- People who have experienced a severe (life threatening) allergy to a prior dose of an seasonal influenza vaccine (TIV or LAIV)
- People who have a severe allergy to a component of the TIV vaccine. Package inserts should be consulted for components 3
Recommendations for vaccinating egg allergic patients were updated in 2011 and are available in the MMWR.8 Generally, egg allergic patients can safely receive TIV. Individuals with a history of severe (life threatening) allergy to eating eggs should consult with a specialist with expertise allergy prior to receiving TIV.
- TIV should not be administered to infants less than 6 months of age.
In general, vaccinations should be deferred when a precaution is present. However, a vaccination might be indicated in the presence of a precaution because the benefit of protection from the vaccine outweighs the risk for an adverse reaction. This is left to the healthcare provider to make a decision. The following are precautions for TIV: 1,4
- Guillain–Barré Syndrome (GBS) within 6 weeks of a previous dose of an influenza vaccine (TIV or LAIV); and
- Presence of a moderate or severe acute illness with or without a fever. Persons who were hospitalized with an acute illness but who are now well enough to be discharged from a hospital can be vaccinated.
Screening Before Vaccination
- Before administering an influenza vaccine, people should be asked about the following: 1,4
- Allergies. Asking the persons if they can eat eggs without adverse effects is a good way to screen for egg allergy;
- Adverse events, including GBS, after prior doses of influenza vaccine; and
- Current health status, including any current (acute) illness.
Safe Vaccine Administration
To reduce the risk of adverse events after vaccination the follow steps should be taken:5
- TIV should be administered by intramuscular injection using appropriate technique.
- Providers vaccinating children and adolescents aged <19 years should be sure the TIV formulation is licensed for use in children in their patients’ age group and the proper dose is used. TIV is not licensed for use in infants aged <6 months.
- Providers should consult the Advisory Committee on Immunization Practices (ACIP) General Recommendations regarding other steps to take that may help prevent adverse events after TIV vaccination.4
Live, Attenuated Influenza Vaccine (LAIV)
Studies support the safety of LAIV. LAIV is administered as an intranasal vaccine and replicates in the nose. Rhinitis (runny nose) and nasal congestion occur more commonly after LAIV than TIV or placebo in adults and children.8 More information is provided below:
- Most common adverse reactions (10% in FluMist and at least 5% greater than in control) are runny nose or nasal congestion in all ages, fever >100F in children 2-6 years of age, and sore throat in adults.9
- One study of 8352 children aged 6 through 59 months showed that the younger children aged 6 through 23 months had increased rates of wheezing in the 42 days after LAIV (6%) than TIV (4%) (LAIV is not licensed for this age group). Children aged 24 through 59 months had similar rates of wheezing after LAIV (2%) and TIV (3%).10
- In children aged 2 through 6 years, fever >100° F occurred more often after first dose LAIV (16%) than placebo (11%).9 Adults receiving LAIV did not have an increased risk for fever after vaccination compared with placebo.9
- In adults the following other adverse events were reported more often after LAIV than after an intranasal placebo: headache, sore throat, tiredness/weakness, muscles aches, cough, chills, and sinusitis.9
LAIV should not be administered to people who have had a severe allergic reaction to the following, unless the person has been desensitized¹
- Severe allergy to eggs.
- Severe allergy to another component of the LAIV vaccine. The package insert should be consulted for components.9
- Severe allergy to a prior dose of an influenza vaccine (TIV or LAIV).
LAIV should also not be administered to people who are in the following groups because the effectiveness or safety of LAIV is not known:
- Children aged <2 years or adults aged ≥50 years
- Pregnant women
- People with known or suspected immunodeficiency diseases or immunosuppressed states (including those caused by HIV)
- Children or adolescents receiving aspirin or other salicylates (because of the association of Reye syndrome with wild-type influenza virus infection)
- People who have other medical conditions that place them at increased risk for complications from influenza, including:
- Asthma or reactive airways disease
- Other chronic disorders of the pulmonary or cardiovascular system (except hypertension)
- Neurological/ neuromuscular diseases
- Metabolic disease, such as diabetes mellitus
- Renal or hepatic dysfunction
The following are precautions for use of LAIV
- Guillain-Barré Syndrome (GBS) within 6 weeks of a previous dose of an influenza vaccine (TIV or LAIV)1
- Presence of a moderate or severe acute illness with or without a fever.5 Persons who were hospitalized with an acute illness but who are now well enough to be discharged from a hospital can be vaccinated.
Screening Before Vaccination
- Before administering an influenza vaccine, people should be asked about the following:1,4
- Allergies. Asking the persons if they can eat eggs without adverse effects is a good way to screen for egg allergy.
- Adverse events, including GBS, after prior doses of influenza vaccine
- Current health status
- Young children may experience episodes of wheezing in association with certain respiratory viruses. Some young children might have a history of wheezing but have not had asthma diagnosed. The following screening recommendations should be used to assist persons who administer influenza vaccines in providing the appropriate vaccine for children aged 2 through 4 years.1
- Screen for possible reactive airways diseases when considering use of LAIV for children aged 2 through 4 years, and avoid use of this vaccine in children with asthma or a recent wheezing episode.
- Consult the medical record, when available, to identify children aged 2 through 4 years with asthma or recurrent wheezing that might indicate asthma.
- Ask parents or caregivers of children aged 2 through 4 years: “In the past 12 months, has a healthcare provider ever told you that your child had wheezing or asthma?”
- Do not administer LAIV to children whose parents or caregivers answer “yes” to this question and children who have asthma or who had a wheezing episode noted in the medical record during the preceding 12 months should not receive LAIV. TIV is available for use in children with asthma or possible reactive airways disease.
Safe Vaccine Administration
- Healthcare providers that are treating severely immunocompromised patients (e.g., patients with hematopoietic stem cell transplants) and close contacts of these patients should receive TIV, rather than LAIV. The rationale for these recommendations is the theoretical risk that a live, attenuated vaccine virus could be transmitted to the severely immunosuppressed person.1
- LAIV should be administered by an intranasal squirt using appropriate technique (see package insert).9
- Providers should consult the ACIP General Recommendations regarding other steps to take that may help prevent adverse events after LAIV vaccination.4
Reporting Adverse Events
- The Vaccine Adverse Event Reporting System (VAERS) is a US vaccine safety surveillance system, co-managed by CDC and FDA.
- VAERS is a post-marketing vaccine safety surveillance program that collects information about reported adverse events that occur after administration of vaccines licensed in the United States.
- VAERS is a key surveillance system used to identify potential vaccine safety concerns. Generally VAERS cannot determine if an adverse event was caused by vaccine but can help determine if further investigations are needed.
- Healthcare providers are encouraged to report all clinically significant adverse events after influenza vaccines and other vaccines to VAERS, even if the healthcare provider is not certain that the vaccine caused the event. Anyone may submit a report to VAERS.
- VAERS reports may be filed securely online (VAERS web site), by mail, or by fax. Report forms are available online or can be obtained by calling 1-800-822-7967 to request reporting forms or other assistance.
- Clinicians and other reporters of adverse events should be encouraged, when submitting a report to VAERS, to include as much information as possible (e.g., vaccination location, date, vaccine type, lot number and dose).
- VAERS data without identifiers may be accessed through the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) public database within about 1 week after CDC receives the VAERS report or for download at the VAERS web site within about 6 weeks after CDC receives the VAERS report.
- Additional information about VAERS is available at the VAERS web site.
The National Vaccine Injury Compensation Program
The National Vaccine Injury Compensation Program (VICP) is a federal program operated by the Health Resources and Services Administration (HRSA). VICP exists to help pay for the care of certain persons found to have had a serious reaction to a vaccine covered by the VICP. For more information about VICP, call 1-800-338-2382 or visit the National Vaccine Injury Compensation Program (VICP) web site.
- Fiore T, Uyeki T, Broder K et al. Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices. 2010. MMWR Recomm Rep. 2010;59:(RR-8):1-66.
- 2012-2013 CDC MMWR: Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP) — United States, 2012–13 Influenza Season.
- Package inserts for influenza vaccines licensed in the United States
- Kroger AT, Sumaya CV, Pickering LK, et al. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011;60:1-64.
- France, EK, Glanz, JM, Xu, S, et al., Safety of the trivalent inactivated influenza vaccine among children: a population-based study. Arch Pediatr Adolesc Med, 2004. 158(11): p. 1031-6.
- Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P. Safety of trivalent inactivated influenza vaccines in adults: Background for pandemic influenza vaccine safety monitoring. Vaccine. 2009:27:2114-2120.
- Tse A, Tseng HF, Greene SK, et al. Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011. Vaccine. 2012;30:2024-31
- Grohskopf L, Uyeki T, Bresee J, et al. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011;60:1128-32.
- FluMist® package insert for 2012-2013 influenza vaccines [536 KB, 22 pages].
- Belshe RB, Edwards KM, Vesikari T, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med 2007;356:685-96.
‡ The study, conducted in the Vaccine Safety Datalink (VSD) assessed for associations between TIV and multiple medically–attended events in the 2 weeks after TIV. After chart review, an increased risk after TIV was observed only for impetigo, which was not considered by the investigators to be medically important.
§ The study was conducted in the Vaccine Adverse Event Reporting System (VAERS) to identify possible safety concerns that might warrant further association; it was not designed to quantify risk of specific adverse events after vaccination.